School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, Jinan, 250012, Shandong, China.
Jinan Stomatological Hospital, Jinan, 250001, Shandong, China.
J Mol Histol. 2021 Aug;52(4):671-680. doi: 10.1007/s10735-021-09976-y. Epub 2021 Apr 27.
Nel-like molecule type 1 (Nell-1) is a secreted protein that plays an important role in osteoinduction in multiple animal models. A previous study has suggested the anti-inflammatory effect of Nell-1 on bone inflammation inhibition. However, its role in pulpitis has not been investigated. The present study aims to explore the effect of human recombinant Nell-1 (Nell-1) on rat pulp inflammation response, and its effect on lipopolysaccharide-induced inflammation in human dental pulp cells and its related intracellular signaling pathways. 30 Wistar rats with healthy non-carious maxillary first molars were chosen, Nell-1 was absorbed onto a sterile collagen sponge and capped onto exposed pulps. The expression of IL-6 and IL-8 were detected by immunohistochemical staining. Human dental pulp cells (hDPCs) were isolated from healthy extracted premolars and third molars. hDPCs were co-cultured with Escherichia coli lipopolysaccharide (LPS), Nell-1 protein, and mitogen-activated protein kinase (MAPK) inhibitors. The expression of pro-inflammatory cytokines and chemokines, such as IL-6 and IL-8, was examined via quantitative real-time PCR and enzyme-linked immunosorbent assay. The results showed that Nell-1 inhibited the inflammatory response of rat pulp. LPS treatment contributed to the expression of inflammatory factors in hDPCs, whereas Nell-1 obviously suppressed the LPS-induced inflammation. p38 MAPK and extracellular signal-regulated kinase (ERK) MAPK inhibitors attenuated the anti-inflammatory effect of hrNell-1, whereas the c-Jun N-terminal kinases (JNK) MAPK inhibitor exerted minimal effect. Therefore Nell-1 could inhibit LPS-induced inflammation in human dental pulp cells, and this effect may be mediated by p38 and ERK MAPK signaling pathways, but not JNK MAPK signaling pathway.
神经细胞分泌蛋白 1 型（Nell-1）是一种分泌蛋白，在多种动物模型中发挥重要的成骨诱导作用。先前的研究表明 Nell-1 具有抑制骨炎症的抗炎作用。然而，其在牙髓炎中的作用尚未被研究。本研究旨在探讨人重组 Nell-1（Nell-1）对大鼠牙髓炎症反应的影响，及其对脂多糖诱导的人牙髓细胞炎症的影响及其相关的细胞内信号通路。选择 30 只具有健康非龋上颌第一磨牙的 Wistar 大鼠，将 Nell-1 吸收到无菌胶原海绵上并覆盖在暴露的牙髓上。通过免疫组织化学染色检测 IL-6 和 IL-8 的表达。从健康拔除的前磨牙和第三磨牙中分离出人牙髓细胞（hDPCs）。将 hDPCs 与大肠杆菌脂多糖（LPS）、Nell-1 蛋白和丝裂原活化蛋白激酶（MAPK）抑制剂共同培养。通过实时定量 PCR 和酶联免疫吸附试验检测促炎细胞因子和趋化因子（如 IL-6 和 IL-8）的表达。结果表明，Nell-1 抑制了大鼠牙髓的炎症反应。LPS 处理促进了 hDPCs 中炎症因子的表达，而 Nell-1 明显抑制了 LPS 诱导的炎症。p38 MAPK 和细胞外信号调节激酶（ERK）MAPK 抑制剂减弱了 hrNell-1 的抗炎作用，而 c-Jun N-末端激酶（JNK）MAPK 抑制剂的作用较小。因此，Nell-1 可以抑制 LPS 诱导的人牙髓细胞炎症，这种作用可能是通过 p38 和 ERK MAPK 信号通路介导的，而不是 JNK MAPK 信号通路。
